Most species have one major histocompatibility complex (MHC); in man it has been called HL-1, in the mouse H-2, and in the rat AgB. The MHC includes markers such as the HL-A, H-2 or AgB antigens, Immune Response (Ir) genes and lymphocyte activating determinants (LAD). It is proposed to develop procedures for the detection and purification of LAD. We will determine their subcellular location, characterize their molecular species and determine their immunogenicity and/or tolerogenicity as they are extracted, or after attachment to a soluble or particulate carrier. We propose to examine the lymphoid populations responding in mixed lymphocyte reactions (MLR) and in cell-mediated immunity (CMI). The studies are relevant to transplantation and to tumor immunology and especially to the cellular immune response against histocompatibility and tumor antigens.